Field of the Invention
The compound, 11-chloro-8,12.beta.-dihydro-2,8-dimethyl-12b-phenyl-4H-[1,3]oxazino[3,2-d ][1,4]benzodiazepine-4,7(6H)-dione, generic name ketazolam, U.S. Pat. No. 3,573,282, is an excellent tranquilizer and anti-anxiety agent which can not only be used for the treatment of the mildly anxious patients, but also for the severely anxious institutionalized patients and for the treatment of alcoholics. Ketazolam has the chemical structure: ##STR1##
This compound is found to be reasonably chemically stable when pure but in the pharmaceutically most convenient formulation, i.e., capsules, which contain the active product with conventional excipients, the stability of ketazolan is greatly reduced.
The present invention is directed to improved formulations of ketazolam which were found to overcome the difficulty encountered by the relative instability of older formulations. Sterotex.RTM., an edible vegetable oil/fat, is used with either calcium lactate or calcium carboxymethylcellulose as the only excipients which provide reasonable stability to the ketazolam in formulations.
A typical set of data comparing the stability of pure ketazolam with formulations is as follows:
______________________________________ % Decomposition Upon Storage at 25.degree. C. Ca-Lactate Base Ca-CMC Base Storage Time Pure drug HFC's HFC's ______________________________________ 3 months 0.255 0.14 0.15 6 months 0.435 0.28 0.285 12 months 0.57 0.68 0.50 ______________________________________
in which
Ca-Lactate is calcium lactate PA1 Ca-CMC is calcium carboxymethyl cellulose PA1 HFC is hard-filled capsules